ERR [alpha] and ERR [gamma] target gene identification by genome-wide : location analysis in the mouse heart

Abstract

Transcriptional regulation by nuclear receptors is vital for a number of different biological processes such as cellular differentiation, embryo development and homeostasis. Recent studies on the roles of estrogen-related receptor alpha (ERRalpha) and gamma (ERRgamma) have demonstrated an important function of these orphan receptors in the control of cardiac energy metabolism. Chromatin immunoprecipitation (ChIP)-on-chip was optimized and then performed using chromatin from mouse hearts on a genome-wide basis to provide further insight into the roles of these ERRs in the heart. In this thesis, we report the identification of ERRalpha and ERRgamma direct target genes in cardiac tissue implicated in various processes such as apoptosis, transcriptional regulation, signal transduction, heart development, electron transport/oxidative metabolism, as well as lipid, carbohydrate, and protein metabolism. However, one important and unexpected outcome of the experiments was the significant number of ERR target genes associated with cardiac hypertrophy in humans